tbuckley/cabot-search huggingface dataset:
Substance Use, Mental Health Challenges Widespread in 2021
Authors: Howard D. Larkin
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Publisher Correction: Gut Parabacteroides merdae protects against cardiovascular damage by enhancing branched-chain amino acid catabolism
Authors: Shanshan Qiao, Chang Liu, Li Sun, Tao Wang, Huanqin Dai, Kai Wang, Li Bao, Hantian Li, Wenzhao Wang, Shuang-Jiang Liu, Hongwei Liu
Journal: Nature Metabolism (2023)
CD200 <sup>+</sup> cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy
Authors: Xinxin Wang, Haoran Zha, Wei Wu, Ting Yuan, Shuanglong Xie, Zheng Jin, Haixia Long, Fei Yang, Zhongyu Wang, Anmei Zhang, Jianbao Gao, Ying Jiang, Lujing Wang, Chunyan Hu, Yisong Y. Wan, Qi-Jing Li, Alistair L. J. Symonds, Qingzhu Jia, Bo Zhu
Journal: Science Translational Medicine (2023)

Anti–PD-1/PD-L1 therapy, either by anti–PD-1 antibody or anti–PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8 + T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8 + T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200 + cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200 + T cells positively related to a favorable clinical outcome to anti–PD-1/PD-L1 therapy in three independent cohorts of patients with cancer. Using multiple mouse tumor models, we demonstrated that CD200 + CTLs are essential for efficacious anti–PD-L1 therapy. Mechanistically, we observed a unique chromatin landscape in CD200 + CTLs and found that these cells are enriched for tumor antigen–specific CTLs and have antitumor effector functions. Coinoculation of CD200 + CTLs with tumor cells led to robust tumor regression in two transplanted mouse models. Clinically, we found that infiltration of CD200 + CTLs into tumors could predict immunotherapy efficacy in six patient cohorts. Together, our findings reveal that CD200 + CTLs in the tumor microenvironment are crucial for efficacious anti–PD-1/PD-L1 therapy and could serve as a predictor of successful immunotherapy in the clinic.
Respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in severe SARS-CoV-2 pneumonia: a multicentre randomized controlled trial
Authors: Muriel Fartoukh, Saad Nseir, Bruno Mégarbane, Yves Cohen, Antoine Lafarge, Damien Contou, Arnaud W. Thille, Louis-Marie Galerneau, Florian Reizine, Martin Cour, Kada Klouche, Jean-Christophe Navellou, Laurent Bitker, Alexandra Rousseau, Sophie Tuffet, Tabassome Simon, Guillaume Voiriot
Journal: Clinical Microbiology and Infection (2023)

We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia.This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28.Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups.In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.
Whole genome sequencing provides comprehensive genetic testing in childhood B-cell acute lymphoblastic leukaemia
Authors: Sarra L. Ryan, John F. Peden, Zoya Kingsbury, Claire J. Schwab, Terena James, Petri Polonen, Martina Mijuskovic, Jenn Becq, Richard Yim, Ruth E. Cranston, Dale J. Hedges, Kathryn G. Roberts, Charles G. Mullighan, Ajay Vora, Lisa J. Russell, Robert Bain, Anthony V. Moorman, David R. Bentley, Christine J. Harrison, Mark T. Ross
Journal: Leukemia (2023)

Abstract Childhood B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by recurrent genetic abnormalities that drive risk-directed treatment strategies. Using current techniques, accurate detection of such aberrations can be challenging, due to the rapidly expanding list of key genetic abnormalities. Whole genome sequencing (WGS) has the potential to improve genetic testing, but requires comprehensive validation. We performed WGS on 210 childhood B-ALL samples annotated with clinical and genetic data. We devised a molecular classification system to subtype these patients based on identification of key genetic changes in tumour-normal and tumour-only analyses. This approach detected 294 subtype-defining genetic abnormalities in 96% (202/210) patients. Novel genetic variants, including fusions involving genes in the MAP kinase pathway, were identified. WGS results were concordant with standard-of-care methods and whole transcriptome sequencing (WTS). We expanded the catalogue of genetic profiles that reliably classify PAX5 alt and ETV6::RUNX1 -like subtypes. Our novel bioinformatic pipeline improved detection of DUX4 rearrangements ( DUX4 -r): a good-risk B-ALL subtype with high survival rates. Overall, we have validated that WGS provides a standalone, reliable genetic test to detect all subtype-defining genetic abnormalities in B-ALL, accurately classifying patients for the risk-directed treatment stratification, while simultaneously performing as a research tool to identify novel disease biomarkers.
Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation
Authors: Burcu Ayoglu, Michele Donato, Daniel E Furst, Leslie J Crofford, Ellen Goldmuntz, Lynette Keyes-Elstein, Judith James, Susan Macwana, Maureen D Mayes, Peter McSweeney, Richard A Nash, Keith M Sullivan, Beverly Welch, Ashley Pinckney, Rong Mao, Lorinda Chung, Purvesh Khatri, Paul J Utz
Journal: Annals of the Rheumatic Diseases (2023)

Results from the SCOT (Scleroderma: Cyclophosphamide Or Transplantation) clinical trial demonstrated significant benefits of haematopoietic stem cell transplant (HSCT) versus cyclophosphamide (CTX) in patients with systemic sclerosis. The objective of this study was to test the hypothesis that transplantation stabilises the autoantibody repertoire in patients with favourable clinical outcomes.
Abstract PR011: TXNRD1 drives innate immune response in senescent cells to promote tumor immune surveillance and age-associated inflammation
Authors: Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Hsin Yao Tang, Aaron Havas, Andrew V. Kossenkov, Shelley Berger, Peter D. Adams, David W. Speicher, Rugang Zhang
Journal: Cancer Research (2023)

Abstract Cellular senescence regulates cancer and tissue aging in part through the secretion of proinflammatory factors known as the senescence-associated secretory phenotype (SASP). For example, sterile inflammation or ‘inflammaging’ is a hallmark of tissue aging. Thioredoxin reductase 1 (TXNRD1) genetic variability is associated with aging and is often upregulated in human cancers. TXNRD1’s role in regulating tissue aging and cancer has been attributed to its enzymatic role in regulating cellular redox. Here we show that TXNRD1 drives the SASP and inflammation through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune response pathway independently of its enzymatic activity. TXNRD1 localizes to cytoplasmic chromatin fragments (CCF) and interacts with cGAS in a senescence status dependent manner, which is required for the SASP. Biochemically, TXNRD1 enhances the enzymatic activity of cGAS. TXNRD1 is required for both the tumor-promoting and immune-surveillance functions of senescent cells, which are mediated by the SASP in vivo in mouse tumor models. Treatment of aged mice with a TXNRD1 inhibitor that disrupts its interaction with cGAS, but not an inhibitor of its enzymatic activity alone, downregulated inflammaging in several tissues. In summary, our results report TXNRD1 promotes inflammation via activating the innate immune response in a manner depending on its interaction with cGAS but not its enzymatic activity. Our findings have important implications for both tissue aging and cancer. Citation Format: Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Hsin Yao Tang, Aaron Havas, Andrew V. Kossenkov, Shelley Berger, Peter D. Adams, David W. Speicher, Rugang Zhang. TXNRD1 drives innate immune response in senescent cells to promote tumor immune surveillance and age-associated inflammation [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr PR011.
The role of different viral biomarkers on the management of chronic hepatitis B
Authors: Lung-Yi Mak, Rex Wan-Hin Hui, James Fung, Wai Kay Seto, Man-Fung Yuen
Journal: Clinical and Molecular Hepatology (2023)

Chronic hepatitis B infection is a major public health challenge. With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for ≥6 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial/ functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use.
Corrigendum to “An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication” [Genomics Proteomics Bioinformatics19 (1) (2021) 108–122]
Authors: Guang Song, Emily M. Lee, Jianbo Pan, Miao Xu, Hee-Sool Rho, Yichen Cheng, Nadia Whitt, Shu Yang, Jennifer Kouznetsova, Carleen Klumpp-Thomas, Samuel G. Michael, Cedric Moore, Ki-Jun Yoon, Kimberly M. Christian, Anton Simeonov, Wenwei Huang, Menghang Xia, Ruili Huang, Madhu Lal-Nag, Hengli Tang, Wei Zheng, Jiang Qian, Hongjun Song, Guo-li Ming, Heng Zhu
Journal: Genomics Proteomics & Bioinformatics (2022)
Nonadherence to immune-modifying therapies during the COVID-19 pandemic: the crucial role of doctor–patient communication in avoiding drug discontinuation
Authors: Mario Valenti, Antonio Costanzo
Journal: British Journal of Dermatology (2023)

Journal Article Nonadherence to immune-modifying therapies during the COVID-19 pandemic: the crucial role of doctor–patient communication in avoiding drug discontinuation Get access Mario Valenti, Mario Valenti Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, ItalyDermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy Search for other works by this author on: Oxford Academic Google Scholar Antonio Costanzo Antonio Costanzo Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, ItalyDermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy Correspondence: Antonio Costanzo. Email: antonio.costanzo@hunimed.eu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 188, Issue 5, May 2023, Pages 586–590, https://doi.org/10.1093/bjd/ljad014 Published: 19 January 2023 Article history Received: 13 January 2023 Published: 19 January 2023 Corrected and typeset: 14 February 2023 Accepted: 23 February 2023
Bone marrow inflammatory memory in cardiometabolic disease and inflammatory comorbidities
Authors: Ioannis Mitroulis, George Hajishengallis, Triantafyllos Chavakis
Journal: Cardiovascular Research (2023)

Abstract Cardiometabolic disorders are chief causes of morbidity and mortality, with chronic inflammation playing a crucial role in their pathogenesis. The release of differentiated myeloid cells with elevated pro-inflammatory potential, as a result of maladaptively trained myelopoiesis may be a crucial factor for the perpetuation of inflammation. Several cardiovascular risk factors, including sedentary lifestyle, unhealthy diet, hypercholesterolemia, and hyperglycemia, may modulate bone marrow hematopoietic progenitors, causing sustained functional changes that favour chronic metabolic and vascular inflammation. In the present review, we summarize recent studies that support the function of long-term inflammatory memory in progenitors of the bone marrow for the development and progression of cardiometabolic disease and related inflammatory comorbidities, including periodontitis and arthritis. We also discuss how maladaptive myelopoiesis associated with the presence of mutated hematopoietic clones, as present in clonal hematopoiesis, may accelerate atherosclerosis via increased inflammation.
Corrigendum to “Ttc21b deficiency attenuates autosomal dominant polycystic kidney disease in a kidney tubular- and maturation-dependent manner.” Kidney Int. 2022;102:577–591
Authors: Wei Wang, Luciane M. Silva, Henry H. Wang, Matthew A. Kavanaugh, Tana S. Pottorf, Bailey A. Allard, Damon T. Jacobs, Rouchen Dong, Joseph T. Cornelius, Aakriti Chaturvedi, Katherine I. Swenson-Fields, Timothy A. Fields, Michele T. Pritchard, Madhulika Sharma, Chad Slawson, Darren P. Wallace, James P. Calvet, Pamela V. Tran
Journal: Kidney International (2023)
Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains
Authors: Anton Spadar, João Perdigão, Susana Campino, Taane G. Clark
Journal: Genome Medicine (2023)

Abstract Background Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden in other geographical regions. Methods Here, we examined the largest collection of publicly available sequenced Kp isolates ( n =13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp. Results We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp ( n =1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones. Conclusions Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally.
Is there a future for maintenance temozolomide chemotherapy in PCNSL?
Authors: Jacoline E C Bromberg, Jeanette K Doorduijn
Journal: Neuro-Oncology (2023)

Journal Article Is there a future for maintenance temozolomide chemotherapy in PCNSL? Get access Jacoline E C Bromberg, Jacoline E C Bromberg Department of Neuro-Oncology, Erasmus MC University Medical Center Cancer Institute, Rotterdam, the Netherlands Corresponding Author: Jacoline E. C. Bromberg, MD, Department of Neuro-Oncology, Erasmus MC Cancer Institute, PO Box 2040, 3000 CA Rotterdam, The Netherlands (j.bromberg@erasmusmc.nl) Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeanette K Doorduijn Jeanette K Doorduijn Department of Hematology, Erasmus MC University Medical Center Cancer Institute, Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 4, April 2023, Pages 699–700, https://doi.org/10.1093/neuonc/noad015 Published: 19 January 2023 Article history Published: 19 January 2023 Corrected and typeset: 13 February 2023
Upper age limits for US male human papillomavirus vaccination for oropharyngeal cancer prevention: a microsimulation-based modeling study
Authors: Rebecca Landy, Gregory Haber, Barry I Graubard, Nicole G Campos, Stephen Sy, Jane J Kim, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Human papillomavirus (HVP)–positive oropharyngeal cancer is the most common HPV-associated cancer in the United States. The age at acquisition of oral HPV infections that cause oropharyngeal cancer (causal infections) is unknown; consequently, the benefit of vaccination of US men aged 27-45 years remains uncertain. Methods We developed a microsimulation-based, individual-level, state-transition model of oral HPV16 and HPV16-positive oropharyngeal cancer among heterosexual US men aged 15-84 years, calibrated to population-level data. We estimated the benefit of vaccination of men aged 27-45 years for prevention of oropharyngeal cancer, accounting for direct- and indirect effects (ie, herd effects) of male and female vaccination. Results In the absence of vaccination, most (70%) causal oral HPV16 infections are acquired by age 26 years, and 29% are acquired between ages 27 and 45 years. Among men aged 15-45 years in 2021 (1976-2006 birth cohorts), status quo vaccination of men through age 26 years is estimated to prevent 95% of 153 450 vaccine-preventable cancers. Assuming 100% vaccination in 2021, extending the upper age limit to 30, 35, 40, or 45 years for men aged 27-45 years (1976-1994 cohorts) is estimated to yield small benefits (3.0%, 4.2%, 5.1%, and 5.6% additional cancers prevented, respectively). Importantly, status quo vaccination of men through age 26 years is predicted to result in notable declines in HPV16-positive oropharyngeal cancer incidence in young men by 2035 (51% and 24% declines at ages 40-44 years and 45-49 years, respectively) and noticeable declines (12%) overall by 2045. Conclusion Most causal oral HPV16 infections in US men are acquired by age 26 years, underscoring limited benefit from vaccination of men aged 27-45 years for prevention of HPV16-positive oropharyngeal cancers.
Covid-19: What do we know about XBB.1.5 and should we be worried?
Authors: Elisabeth Mahase
Journal: BMJ (2023)

Covid-19: What do we know about XBB.1.5 and should we be worried?The XBB.1.5omicron variant of SARS-CoV-2 has been making headlines for weeks.Elisabeth Mahase reports what we know so far Elisabeth Mahase
Diet–microbial cross–talk underlying increased visceral perception
Authors: Giada De Palma, David E. Reed, Premysl Bercik
Journal: Gut Microbes (2023)

Visceral hypersensitivity, a fundamental mechanism of chronic visceral pain disorders, can result from both central or peripheral factors, or their combination. As an important regulator of normal gut function, the gut microbiota has been implicated as a key peripheral factor in the pathophysiology of visceral hypersensitivity. Patients with chronic gastrointestinal disorders, such as irritable bowel syndrome, often present with abdominal pain secondary to adverse reactions to dietary components. As both long- and short-term diets are major determinants of gut microbiota configuration that can result in changes in microbial metabolic output, it is becoming increasingly recognized that diet-microbiota interactions play an important role in the genesis of visceral sensitivity. Changes in pain signaling may occur via diet-induced changes in secretion of mediators by both the microbiota and/or host cells. This review will examine the peripheral influence of diet-microbiota interactions underlying increased visceral sensitivity.
Assessing—and Extending—California’s Insulin Manufacturing Initiative
Authors: Jacob S. Sherkow, Eli Y. Adashi, I. Glenn Cohen
Journal: JAMA (2023)

This Viewpoint reviews California’s recently proposed CalRx initiative to manufacture biosimilar insulin, highlights challenges facing the initiative, and suggests ways in which, if successful, the initiative could serve as a model for state-managed development of drugs other than insulin, reduce drug prices, and provide other benefits.